We propose to develop and apply methods for measurement of 1,6-hexamethylene diisocyanate (HDI) exposure of spray painters who are at risk for sensitization and development of occupational asthma. The importance of the problem and the availability of a well-defined "at-risk" study population warrant the comprehensive nature of this proposed research. To achieve this goal, we will recruit 50 spray painters from one U.S. Marine/Navy base. Personal breathing-zone exposure will be measured with the Iso-Check TM sampler. Blood and urine samples will be analyzed for the metabolite 1,6-hexamethylene diamine (HDA) as a marker for whole body exposure and systemic absorption. Dermal deposition and penetration into the stratum corneum will be measured using a non-invasive tape-stripping method. An enzyme-linked immunosorbent assay (ELISA) method for detection of HDI-adducted keratin will be developed in order to measure HDI absorption and the potential systemic bioavailability via the skin. Development of the capacity to measure adducts of HDI in the skin will allow us to define the kinetics and dosimetry of exposure(s). We will correlate the measured dermal concentration by the developed methods (ELISA and/or HDI extracted from the keratinized skin) with concentrations in other sentinel media (HDA in urine or plasma). Together, these data will allow us to correlate dermal exposure to systemic exposure and to determine the significance of exposure through the skin. Correlation between the biologically available dose and the dose measured in the biological specimens is critical to developing an understanding of the role of HDI exposure through the skin. Finally, we will be able to determine how factors related to job classification and work tasks affect recent dermal exposure to HDI in occupationally exposed workers using mixed-effects linear-regression models and to develop a model for spray painting exposure to predict dermal deposition rates and to evaluate these predictions in laboratory and field settings. By combining a industrial hygiene survey with measurements of exposure through all potential routes, with measurements of biologically available dose and sophisticated exposure modeling, the methods developed and results obtained by this study will be valuable for understanding of the role of dermal exposure as a vehicle for systemic exposure and for developing strategies to measure and minimize dermal exposure.